Adenosine-producing regulatory B cells in head and neck cancer.

Cancer Immunology, Immunotherapy : CII
Sandra JeskePatrick J Schuler

Abstract

Multiple mechanisms of immunosuppression have been identified in the tumor microenvironment including regulatory B cells (Breg). Recently, we have shown that Breg suppress T cell function by production of adenosine (ADO). However, the autocrine effect of ADO on B cells and the role of Breg in head and neck cancer remains unclear. Blood (n = 42) and tumor tissue (n = 39) of head and neck cancer patients and healthy donors (n = 60) were analyzed by FACS. The effect of ADO on phenotype, intracellular signaling pathways, Ca2+ influx and ADO production was analyzed in Breg and effector B cells (Beff) by FACS, luminescence and mass spectrometry. The blockage of the ADO receptor A2A was analyzed in a murine head and neck cancer model. ADO-producing Breg were found in tumor tissue and peripheral blood. ADO inhibited the intracellular Bruton's tyrosine kinase (BTK) and Ca2+ influx only in Beff. The inhibition of BTK by ibrutinib mimicked the effect of ADO, and ibrutinib reduced the production of ADO by downregulation of CD39 in vitro. The inhibition of ADO receptor A2A significantly reduced tumor mass and increased B cell infiltration, in vivo. Our data demonstrate the presence of a novel ADO-producing Breg population within the tumor m...Continue Reading

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Citations

Aug 6, 2020·Cancers·Jan C SchroederPatrick J Schuler
Jan 20, 2021·Cellular and Molecular Life Sciences : CMLS·Aneesha Kulkarni, Laura W Bowers
Nov 17, 2020·Frontiers in Immunology·Jin ShangYufa Sun
May 5, 2021·Expert Review of Proteomics·Jamile De Oliveira SáAdriana Franco Paes Leme

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Methods Mentioned

BETA
flow cytometry
FACS

Clinical Trials Mentioned

NCT02403193
NCT02503774

Software Mentioned

GraphPad Prism
Kaluza flow cytometry
Excel

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